Melphalan cytotoxicity to murine L1210 cells is dependent upon uptake via two amino acid transport systems. Murine bone marrow progenitor cells lack one of the two amino acid transport systems present in murine L1210 leukemia cells. Specifically, this sensitive host tissue lacks the high-affinity, leucine-preferring system which is sensitive to 2-amino-bicyclo(2,2,1) heptane-2-carboxylic acid. Examination of ability of cyclic amino acids to block melphalan cytotoxicity which is mediated through the tumor specific transport system indicated that tricyclic is greater than bicyclic is greater than monocyclic and suggests that synthesis of bis(chloroethyl) amino derivatives of tricyclic amino acids may result in antitumor agents which exhibit less myelosuppression due to their uptake by a tumor-specific amino acid transport system. The basic amino acids increase intracellular levels of melphalan by antagonizing the increase in melphalan efflux provided by leucine. The increase in intracellular melphalan provided by the basic amino acids occurred solely through the monovalent cation-dependent transport system and not through system L.